Epinephrine

6 ADVERSE REACTIONS Due to the lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below. Common adverse reactions to systemically administered epinephrine include anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache; and/or respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism [ see Warnings and Precautions (5.5) ]. Cardiovascular Reactions Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or those receiving certain drugs [see Warnings and Precautions (5.5) and Drug Interactions (7) ] . Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions (5.5) ] . Angina may occur in patients with coronary artery disease [see Warnings and Precautions (5.5) ] . Rare cases of stress cardiomyopathy have been reported in patients treated with epinephrine. Reactions from Accidental Injection and/or Improper Technique Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions (5.2) ] . Adverse reactions experienced as a result of accidental injections may include increased heart rate, local reactions including injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury. Lacerations, bent needles, and embedded needles have been reported when epinephrine injection, USP auto-injector has been injected into the thigh of young children who are uncooperative and kick or move during the injection [see Warning and Precautions (5.2) ] . Injection into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions (5.2) ]. Skin and Soft Tissue Infections Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection, including epinephrine injection, USP auto-injector, in the thigh [see Warnings and Precautions (5.3) ] . Adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

4 CONTRAINDICATIONS None None ( 4 )

11 DESCRIPTION Epinephrine injection, USP auto-injectors, 0.3 mg and 0.15 mg, are single-dose auto-injectors and combination products containing drug and device components. Each epinephrine injection, USP auto-injector, 0.3 mg delivers a single dose of 0.3 mg epinephrine from epinephrine injection, USP 0.3 mg/0.3 mL in a sterile solution. Each epinephrine injection, USP auto-injector, 0.15 mg delivers a single dose of 0.15 mg epinephrine from epinephrine injection, USP 0.15 mg/0.3 mL in a sterile solution. Each 0.3 mL in the epinephrine injection, USP auto-injector, 0.3 mg contains 0.3 mg epinephrine, 1.8 mg sodium chloride, 0.5 mg sodium metabisulfite, hydrochloric acid to adjust pH, and Water for Injection. The pH range is 2.2-5.0. Each 0.3 mL in the epinephrine injection, USP auto-injector, 0.15 mg contains 0.15 mg epinephrine, 1.8 mg sodium chloride, 0.5 mg sodium metabisulfite, hydrochloric acid to adjust pH, and Water for Injection. The pH range is 2.2-5.0. Epinephrine is a sympathomimetic catecholamine. Chemically, epinephrine is (-)-3,4- Dihydroxy-α-[(methylamino)methyl]benzyl alcohol with the following structure: Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin. Replace epinephrine injection, USP auto-injector if the epinephrine solution appears discolored (pinkish or brown color), cloudy, or contains particles. Thoroughly review the patient instructions and operation of epinephrine injection, USP auto-injector with patients and caregivers prior to use [ see Patient Counseling Information (17) ]. Epinephrine Structrual Formula

2 DOSAGE AND ADMINISTRATION Patients greater than or equal to 30 kg (66 lbs): epinephrine injection, USP auto-injector , 0.3 mg ( 2 ) Patients 15 to 30 kg (33 lbs to 66 lbs): epinephrine injection, USP auto-injector, 0.15 mg ( 2 ) Inject intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Each device is a single-dose injection. ( 2 ) 2.1 Recommended Dosage According to Patient Body Weight Patients greater than or equal to 30 kg (approximately 66 pounds or more): epinephrine injection, USP auto-injector, 0.3 mg Patients 15 kg to 30 kg (33 pounds to 66 pounds): epinephrine injection, USP auto-injector, 0.15 mg 2.2 Administration Instructions Inject the single-dose epinephrine injection, USP auto-injector intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Do not inject intravenously, and do not inject into buttocks, into digits, hands or feet [see Warnings and Precautions (5.2) ]. Instruct caregivers of young children who are prescribed an epinephrine injection, USP auto-injector and who may be uncooperative and kick or move during an injection to hold the leg firmly in place and limit movement prior to and during an injection [see Warnings and Precautions (5.2) ] . Each epinephrine injection, USP auto-injector is a single-dose epinephrine injection for single use. Since the doses of epinephrine delivered from epinephrine injection, USP auto-injector are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary. With severe persistent anaphylaxis, repeat injections with an additional epinephrine injection, USP auto-injector may be necessary. More than two sequential doses of epinephrine should only be administered under direct medical supervision [see Warnings and Precautions (5.1) ] . The epinephrine solution in the clear window of the additional epinephrine injection, USP auto-injector should be inspected visually for particulate matter and discoloration. Discarding After Use: The epinephrine injection, USP contains 2 mL epinephrine solution. Approximately 1.7 mL remains in the auto-injector after activation, but is not available for future use, and should be discarded .

1 INDICATIONS AND USAGE Epinephrine injection, USP auto-injectors are indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. Epinephrine injection, USP auto-injectors are intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions. Anaphylactic reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria or angioedema. Epinephrine injection, USP auto-injectors are intended for immediate administration as emergency supportive therapy only and are not a substitute for immediate medical care. Epinephrine injection, USP auto-injector is a non-selective alpha and beta-adrenergic receptor agonist indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis. ( 1 )

10 OVERDOSAGE Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Treatment consists of rapidly acting vasodilators or alpha-adrenergic blocking drugs and/or respiratory support. Epinephrine overdosage can also cause transient bradycardia followed by tachycardia, and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug such as propranolol. Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis, and kidney failure. Suitable corrective measures must be taken in such situations.

7 DRUG INTERACTIONS Cardiac Glycosides, Diuretics, and Anti-arrhythmics Patients who receive epinephrine while concomitantly taking cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias [ see Warnings and Precautions (5.5) ]. Antidepressants, Monoamine Oxidase Inhibitors, Levothyroxine, and Antihistamines The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine. Beta-Adrenergic Blockers The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta- adrenergic blocking drugs, such as propranolol. Alpha-Adrenergic Blockers The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha- adrenergic blocking drugs, such as phentolamine. Ergot Alkaloids Ergot alkaloids may also reverse the pressor effects of epinephrine. Cardiac glycosides or diuretics: observe for development of cardiac arrhythmias. ( 7 ) Tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines: potentiate effects of epinephrine. ( 7 ) Beta-adrenergic blocking drugs antagonize cardiostimulating and bronchodilating effects of epinephrine. ( 7 ) Alpha-adrenergic blocking drugs antagonize vasoconstricting and hypertensive effects of epinephrine. ( 7 ) Ergot alkaloids may reverse the pressor effects of epinephrine. ( 7 )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Epinephrine acts on both alpha- and beta-adrenergic receptors. 12.2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. When given subcutaneously or intramuscularly, epinephrine has a rapid onset and short duration of action.

12.1 Mechanism of Action Epinephrine acts on both alpha- and beta-adrenergic receptors.

12.2 Pharmacodynamics Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder. When given subcutaneously or intramuscularly, epinephrine has a rapid onset and short duration of action.

20231109

1

3 DOSAGE FORMS AND STRENGTHS Injection: 0.3 mg (0.3 mg/0.3 mL), clear and colorless solution in single-dose pre-filled auto-injector Injection: 0.15 mg (0.15 mg/0.3 mL), clear and colorless solution in single-dose pre-filled auto-injector Injection: 0.3 mg (0.3 mg/0.3 mL) single-dose pre-filled auto-injector ( 3 ) Injection: 0.15 mg (0.15 mg/0.3 mL) single-dose pre-filled auto-injector ( 3 )

Epinephrine Epinephrine SODIUM CHLORIDE SODIUM METABISULFITE HYDROCHLORIC ACID WATER EPINEPHRINE EPINEPHRINE

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage (1) ]. The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro . Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage (1) ]. The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

NDA019430

Epinephrine

Epinephrine

70518-1910

HUMAN PRESCRIPTION DRUG

INTRAMUSCULAR

DRUG: Epinephrine GENERIC: Epinephrine DOSAGE: INJECTION ADMINSTRATION: INTRAMUSCULAR NDC: 70518-1910-0 PACKAGING: 0.3 mL in 1 SYRINGE, GLASS OUTER PACKAGING: 1 in 1 CONTAINER OUTER PACKAGING: 2 in 1 CARTON ACTIVE INGREDIENT(S): EPINEPHRINE 0.15mg in 0.3mL INACTIVE INGREDIENT(S): SODIUM CHLORIDE SODIUM METABISULFITE HYDROCHLORIC ACID WATER Remedy_Label

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling ( Patient Information and Instructions for Use ). A healthcare provider should review the patient instructions and operation of epinephrine injection, USP auto-injector in detail, with the patient or caregiver. Epinephrine is essential for the treatment of anaphylaxis. Patients who are at risk of or with a history of severe allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs, and other allergens, as well as idiopathic and exercise-induced anaphylaxis, should be carefully instructed about the circumstances under which epinephrine should be used. Administration Instruct patients and/or caregivers in the appropriate use of epinephrine injection, USP auto-injector. Epinephrine injection, USP auto-injector should be injected into the middle of the outer thigh (through clothing, if necessary). Each device is a single-use injection. Advise patients to seek immediate medical care in conjunction with administration of epinephrine injection, USP auto-injectors. Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection. Lacerations, bent needles, and embedded needles have been reported when epinephrine injection, USP auto-injector has been injected into the thigh of young children who are uncooperative and kick or move during an injection [ see Warnings and Precautions (5.2) ]. Instruct patients and/or caregivers to throw away the blue safety release immediately after using epinephrine injection, USP auto-injector. This small part may pose a choking hazard for children. Complete patient information, including dosage, directions for proper administration and precautions can be found inside each epinephrine injection, USP auto-injector carton. A printed label on the surface of epinephrine injection, USP auto-injector shows instructions for use and a diagram depicting the injection process. Training Instruct patients and/or caregivers to use and practice with the Trainer to familiarize themselves with the use of epinephrine injection, USP auto-injector in an allergic emergency. The Trainer may be used multiple times. A Trainer device is provided in epinephrine injection, USP auto-injector cartons. Instruct patients and/or caregivers to immediately place the blue safety release back on the Trainer and reset it after practicing. This small part may pose a choking hazard for children. Adverse Reactions Epinephrine may produce symptoms and signs that include an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These signs and symptoms usually subside rapidly, especially with rest, quiet and recumbency. Patients with hypertension or hyperthyroidism may develop more severe or persistent effects, and patients with coronary artery disease could experience angina. Patients with diabetes may develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms [ see Warnings and Precautions (5.5) ] . Accidental Injection Advise patients to seek immediate medical care in the case of accidental injection. Since epinephrine is a strong vasoconstrictor when injected into the digits, hands, or feet, treatment should be directed at vasodilatation if there is such an accidental injection to these areas [ see Warnings and Precautions (5.2) ]. Serious Infections at the Injection Site Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site [ see Warnings and Precautions (5.3) ]. Storage and Handling Instruct patients to inspect the epinephrine solution visually through the clear window of the auto-injector periodically. Replace epinephrine injection, USP auto-injector if the epinephrine solution appears discolored (pinkish or brown color), cloudy, or contains particles. Epinephrine is light sensitive and should be stored in the carrier tube provided to protect it from light. The carrier tube is not waterproof. Instruct patients that epinephrine injection, USP auto-injector must be used or properly disposed once the blue safety release is removed or after use [ see Storage and Handling (16) ]. Advise patients and caregivers to give used epinephrine injection, USP auto-injectors to their healthcare provider for inspection and proper disposal. Advise patients and caregivers to promptly dispose of medicines that are no longer needed. Dispose of expired, unwanted, or unused epinephrine injection, USP auto-injectors in an FDA-cleared sharps container. Instruct patients not to dispose epinephrine injection, USP auto-injectors in their household trash. Instruct patients that if they do not have a FDA-cleared sharps disposal container, they may use a household container that is made of a heavy-duty plastic, can be closed with a tight-fitting and puncture-resistant lid without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. Inform patients that they can visit the FDA website for additional information on disposal of unused medicines. Complete patient information, including dosage, directions for proper administration and precautions can be found inside each epinephrine injection, USP auto-injector carton. Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762

INSTRUCTIONS FOR USE Epinephrine Injection [/eh-puh-neh-fruhn/], USP Auto-Injector 0.3 mg one dose of 0.3 mg epinephrine, USP 0.3 mg/0.3 mL for intramuscular and subcutaneous use Epinephrine Injection [/eh-puh-neh-fruhn/], USP Auto-Injector 0.15 mg one dose of 0.15 mg epinephrine, USP 0.15 mg/0.3 mL for intramuscular and subcutaneous use This Instructions for Use contains information on how to administer the epinephrine injection, USP auto-injector. Important Information You Need to Know Before Administering the Epinephrine Injection, USP Auto-Injector The single-dose epinephrine injection, USP auto-injector is for allergic emergency (anaphylaxis) and should be used right away. You can use a second epinephrine injection, USP auto-injector if symptoms continue or symptoms come back. Before you need to use your epinephrine injection, USP auto-injector, make sure your healthcare provider shows you the right way to use it. Anyone who may be able to administer the epinephrine injection, USP auto-injector should also understand how to use it. Carefully read the Instructions for Use in a non-emergency situation and make sure you understand them before using your epinephrine injection, USP auto-injector. If you have any questions, ask your healthcare provider. It is very important that you hold the epinephrine injection, USP auto-injector down for at least 3 full seconds. If you do not hold it in place long enough, the epinephrine injection, USP auto-injector might not have time to deliver the correct dose of medicine. Make sure to always carry 2 epinephrine injection, USP auto-injectors. One dose may not be enough. Inject epinephrine injection, USP auto-injector into the muscle (intramuscular) or under the skin (subcutaneous) in the middle of the outer thigh (see Figure B ). Do not inject epinephrine injection, USP auto-injector into any other part of the body. The injection can be given through clothes. Each epinephrine injection, USP auto-injector can be used only 1 time (single-use). It is normal for most of the medicine to remain in the auto-injector after the dose is injected. The correct dose has been administered if the orange needle end is extended to cover the needle and the medicine viewing window is blocked. Warning: Do not flip the blue safety top off using a thumb or by pulling it sideways, or by bending and twisting the blue safety top. This may cause the device to activate by accident: a “pop” is heard, the orange needle end is extended and the medicine viewing window is blocked. A device that has been activated by accident cannot be used in an emergency. If this happens, replace it with a new epinephrine injection, USP auto-injector. Do not take the epinephrine injection, USP auto-injector apart. Keep the blue safety top in place until you are ready to inject. Always point the orange needle end down (see Figure C ). Keep your fingers, thumb and hand away from the orange needle end. Accidental injection in the fingers, thumb or feet may cause loss of blood flow to these areas. Checking the Blue Safety Top When receiving an epinephrine injection, USP auto-injector and before you need to use the epinephrine injection, USP auto-injector, do the following: Remove the epinephrine injection, USP auto-injector from the protective case and check the auto-injector to make sure the blue safety top is not raised (see Figure D ). If the blue safety top is not raised, the auto-injector is okay to use. Put the auto-injector back in the protective case so that it is ready to be used in an allergic emergency. If the blue safety top is raised (see Figure E), the auto-injector should not be used because the device could activate by accident. Do not try to push the blue safety top back down. Put the auto-injector back in the protective case and replace it with a new epinephrine injection, USP auto-injector. Preparing to Inject Epinephrine Injection, USP Auto-Injector Note the following while preparing to inject epinephrine injection, USP auto-injector: Remove anything in or around the injection site that blocks you from giving the injection. Check the auto-injector before use. If the auto-injector appears damaged, throw it away (dispose of) and do not use. The gray trainer contains no medicine and no needle. Practice with the gray trainer before an allergic emergency happens to make sure you can safely use the real epinephrine injection, USP auto-injector in an emergency. Keep the trainer and the real epinephrine injection, USP auto-injectors away from young children. The epinephrine injection, USP auto-injectors and trainer are not toys. Use by young children should be supervised by an adult. While preparing to inject, make sure you know where to inject (see Figure B ) and how to hold the epinephrine injection, USP auto-injector (see Figure C ). Epinephrine injection, USP auto-injectors have a Never-See-Needle® that covers the needle before and after you inject (see Figure G ). You should never see a needle. If you can see a needle, do not use the epinephrine injection, USP auto-injector. Make sure the epinephrine injection, USP auto-injector has not been used. If an epinephrine injection, USP auto-injector has been used: the orange needle end will be extended (see Step 4 ), the medicine viewing window will be blocked, and the epinephrine injection, USP auto-injector will no longer fit in the protective case. Preparing to Inject a Child If you are giving epinephrine injection, USP auto-injector to a young child, first hold the child firmly in place (restrain) and then use both hands to remove the blue safety top as shown (see Figure J ). Use one hand to hold the auto-injector with the orange needle end pointing down and your other hand to remove the blue safety top to activate the auto-injector. Then, inject in the middle of the outer thigh (see Figure L ). Remember to hold the leg firmly in place before and during the 3 second injection to avoid needlestick injuries including cuts to the thigh. Keep the trainer and the real epinephrine injection, USP auto-injectors away from young children. The real epinephrine injection, USP auto-injectors and trainer are not toys. Use by young children should be supervised by an adult. Checking the Medicine Color Examine the liquid in the medicine viewing window of your epinephrine injection, USP auto-injector regularly. See the information below: Medicine Color: The medicine can be seen through the medicine viewing window located near the middle of the epinephrine injection, USP auto-injector. To check the medicine color, hold the auto-injector in front of a white background in a well-lit area and look through the medicine viewing window. Figure H. Medicine Viewing Window Use the medicine if it is clear and colorless. Do not use the medicine if it is discolored (pinkish or brown color) or if the medicine has particles floating in it. Throw it away (dispose of) and use a new epinephrine injection, USP auto-injector (see the section “Disposing of an Expired, Unused or Used Epinephrine Injection, USP Auto-Injector” on the Patient Information side of this leaflet). Injecting Epinephrine Injection, USP Auto-Injector Step 1 Slide the epinephrine injection, USP auto-injector out of the case (Figure I) Remove the auto-injector from the protective case. Step 2 Pull off the blue safety top (Figure J) Grip the epinephrine injection, USP auto-injector with one hand and with the orange needle end pointing down. Use the other hand to remove the blue safety top. Pull it straight up and away. Note: Do not twist or bend the blue safety top. Failure to pull out the blue safety top correctly (straight up and away) can cause accidental activation. Note: To avoid an accidental injection, never put your thumb, fingers or hand over the orange needle end. If an accidental injection happens, get emergency medical help right away. Step 3 Inject the medicine by self (Figure K) or caregiver (Figure L) administration Place the orange needle end against the outer thigh, through clothing if needed. Push down firmly and hold in place for 3 seconds. Note: Epinephrine injection, USP auto-injectors make a distinct pop sound when pushed against the thigh. This is normal and means that the epinephrine injection, USP auto-injector is working. After the pop, continue to press the epinephrine injection, USP auto-injector down firmly on the outer thigh for 3 seconds to make sure that the medicine is given. Step 4 Check if used (Figure M) Lift the auto-injector straight out from the thigh. The orange needle end will extend to cover the needle. If the needle is visible, do not reuse it. Use a new auto-injector. Throw away the blue safety top. Step 5 Get emergency medical help After injecting epinephrine injection, USP auto-injector, get emergency medical help right away. You can use a second epinephrine injection, USP auto-injector if symptoms continue or come back. Take your used epinephrine injection, USP auto-injector to your healthcare provider. Epinephrine injection, USP auto-injectors are single-dose auto-injectors and cannot be reused. If the needle is visible, do not try to reuse it. Storing Epinephrine Injection, USP Auto-Injector Store the epinephrine injection, USP auto-injectors at room temperature between 68˚ F to 77˚ F (20˚ C to 25˚ C). Keep protective case in the outer carton to protect from light. When exposed to air or light, the medicine in the epinephrine injection, USP auto-injector changes rapidly to a pinkish or brown color and should not be used. Disposing of Epinephrine Injection, USP Auto-Injector After using your epinephrine injection, USP auto-injector, get emergency medical help right away. Take your used auto-injector with you to give to your healthcare provider for disposal. Important: The blue safety top is a small part that may become a choking hazard for children. Throw away the blue safety top immediately after using the epinephrine injection, USP auto-injector. Your epinephrine injection, USP auto-injector has an expiration date. Replace it before the expiration date. For more information on how to throw away (dispose of) your expired epinephrine injection, USP auto-injector, see the section “Disposing of an Expired, Unused or Used Epinephrine Injection, USP Auto-Injector” on the Patient Information side of this leaflet. Manufactured for: Mylan Specialty L.P., Morgantown, WV 26505, U.S.A. by Meridian Medical Technologies, LLC, St. Louis, MO 63146, U.S.A. EpiPen® or EpiPen Jr® are registered trademarks of Mylan Inc., a Viatris Company. Copyright © 2022 Meridian Medical Technologies. All rights reserved. MS:PIL:EPIG:R7 0002190 This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. Revised: 02/2023 Epinephrine Injection, USP Auto-Injector 0.3 mg one dose of 0.3 mg epinephrine, USP 0.3 mg/0.3 mL Epinephrine Injection, USP Auto-Injector 0.15 mg one dose of 0.15 mg epinephrine, USP 0.15 mg/0.3 mL For more information about epinephrine injection, USP auto-injectors and proper use of the product, call Mylan at 1-877-446-3679 or visit www.epipen.com . Figure A Figure B Figure C Figure D and Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M

8.5 Geriatric Use Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, epinephrine injection, USP auto-injector should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [ see Warnings and Precautions (5.5) , Overdosage (10) ].

8.4 Pediatric Use Epinephrine injection, USP auto-injector may be administered to pediatric patients at a dosage appropriate to body weight [ see Dosage and Administration (2.1) ] . Clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from epinephrine injection, USP auto-injectors are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary.

8.1 Pregnancy Risk Summary There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Data Animal Data In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).

8 USE IN SPECIFIC POPULATIONS Elderly patients may be at greater risk of developing adverse reactions. ( 5.5 , 8.5 ) 8.1 Pregnancy Risk Summary There are no adequate and well controlled studies of the acute effect of epinephrine in pregnant women. In animal reproductive studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended human intramuscular and subcutaneous dose on a mg/m 2 basis. Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans. Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries. Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. Data Animal Data In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day). 8.2 Lactation Risk Summary There is no information on the presence of epinephrine in human milk, the effects on breastfed infants, or the effects on milk production. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and non-breastfeeding patients. 8.4 Pediatric Use Epinephrine injection, USP auto-injector may be administered to pediatric patients at a dosage appropriate to body weight [ see Dosage and Administration (2.1) ] . Clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. Since the doses of epinephrine delivered from epinephrine injection, USP auto-injectors are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary. 8.5 Geriatric Use Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, epinephrine injection, USP auto-injector should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [ see Warnings and Precautions (5.5) , Overdosage (10) ].

16 HOW SUPPLIED/STORAGE AND HANDLING Epinephrine Injection, USP Auto-Injectors, 0.15 mg 2-Pak is supplied with 2 single-dose pre-filled auto-injectors and 1 auto-injector trainer device: 0.15 mg/0.3 mL NDC: 70518-1910-00 PACKAGING: 2 in 1 CARTON, 1 in 1 CONTAINER, 0.3 mL in 1 SYRINGE GLASS Storage and Handling • Protect from light. Epinephrine is light sensitive and should be stored in the carrier tube provided to protect it from light. • Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. • Do not refrigerate. • Before using, check to make sure the solution in the auto-injector is clear and colorless. • Replace the auto-injector if the solution is discolored (pinkish or brown color), cloudy, or contains particle. • Properly dispose all used, unwanted or expired epinephrine injection, USP auto-injectors. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762